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1.
J Cereb Blood Flow Metab ; 40(2): 298-313, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30398083

RESUMO

Neurovascular coupling (through which local cerebral blood flow changes in response to neural activation are mediated) is impaired in many diseases including diabetes. Current preclinical rodent models of neurovascular coupling rely on invasive surgery and instrumentation, but transgenic zebrafish coupled with advances in imaging techniques allow non-invasive quantification of cerebrovascular anatomy, neural activation, and cerebral vessel haemodynamics. We therefore established a novel non-invasive, non-anaesthetised zebrafish larval model of neurovascular coupling, in which visual stimulus evokes neuronal activation in the optic tectum that is associated with a specific increase in red blood cell speed in tectal blood vessels. We applied this model to the examination of the effect of glucose exposure on cerebrovascular patterning and neurovascular coupling. We found that chronic exposure of zebrafish to glucose impaired tectal blood vessel patterning and neurovascular coupling. The nitric oxide donor sodium nitroprusside rescued all these adverse effects of glucose exposure on cerebrovascular patterning and function. Our results establish the first non-mammalian model of neurovascular coupling, offering the potential to perform more rapid genetic modifications and high-throughput screening than is currently possible using rodents. Furthermore, using this zebrafish model, we reveal a potential strategy to ameliorate the effects of hyperglycemia on cerebrovascular function.

2.
Transl Stroke Res ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705427

RESUMO

Morphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1 year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1-3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termed cavitation index, as the ratio of the 1-year T1-weighted cavity volume to the baseline RSSI volume on FLAIR. We calculated fractional anisotropy and mean diffusivity (MD) of the RSSI and normal-appearing white matter, and BBB leakage in different tissues on dynamic contrast-enhanced MRI. Amongst 60 patients, at 1-year post-stroke, 44 patients showed some degree of RSSI cavitation on FLAIR, increasing to 50 on T2- and 56 on T1-weighted high-resolution scans, with a median cavitation index of 7% (range, 1-36%). Demographic, clinical, and cerebral small vessel disease features were not associated with the cavitation index. While lower baseline MD of the RSSI (rs = - 0.371; p = 0.004) and more contrast leakage into CSF (rs = 0.347; p = 0.007) were associated with the cavitation index in univariable analysis, only BBB leakage in CSF remained independently associated with cavitation (beta = 0.315, p = 0.046). Increased BBB leakage into CSF may indicate worse endothelial dysfunction and increased risk of tissue destruction post RSSI. Although cavitation was common, it only affected a small proportion of the original RSSI.

3.
Magn Reson Imaging ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31730881

RESUMO

Cerebral small vessel disease (SVD) comprises various pathological processes affecting small brain vessels and damaging white and grey matter. In this paper, we propose a framework comprising region of interest sampling, dynamic spectral and texture description, functional principal component analysis, and statistical analysis to study exogenous contrast agent distribution over time in various brain regions in patients with recent mild stroke and SVD features.We compared our results against current semi-quantitative surrogates of dysfunction such as signal enhancement area and slope. Biological sex, stroke lesion type and overall burden of white matter hyperintensities (WMH) were significant predictors of intensity, spectral, and texture features extracted from the ventricular region (p-value < 0.05), explaining between a fifth and a fourth of the data variance (0.20 ≤Adj.R2 ≤ 0.25). We observed that spectral feature reflected more the dysfunction compared to other descriptors since the overall WMH burden explained consistently the power spectra variability in blood vessels, cerebrospinal fluid, deep grey matter and white matter. Our preliminary results show the potential of the framework for the analysis of dynamic contrast-enhanced brain magnetic resonance imaging acquisitions in SVD since significant variation in our metrics was related to the burden of SVD features. Therefore, our proposal may increase sensitivity to detect subtle features of small vessel dysfunction. A public version of the code will be released on our research website.

4.
EMBO Rep ; 20(8): e47047, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31379129

RESUMO

We identify a novel endothelial membrane behaviour in transgenic zebrafish. Cerebral blood vessels extrude large transient spherical structures that persist for an average of 23 min before regressing into the parent vessel. We term these structures "kugeln", after the German for sphere. Kugeln are only observed arising from the cerebral vessels and are present as late as 28 days post fertilization. Kugeln do not communicate with the vessel lumen and can form in the absence of blood flow. They contain little or no cytoplasm, but the majority are highly positive for nitric oxide reactivity. Kugeln do not interact with brain lymphatic endothelial cells (BLECs) and can form in their absence, nor do they perform a scavenging role or interact with macrophages. Inhibition of actin polymerization, Myosin II, or Notch signalling reduces kugel formation, while inhibition of VEGF or Wnt dysregulation (either inhibition or activation) increases kugel formation. Kugeln represent a novel Notch-dependent NO-containing endothelial organelle restricted to the cerebral vessels, of currently unknown function.

5.
Clin Gastroenterol Hepatol ; 17(13): 2678-2686.e2, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30885888

RESUMO

BACKGROUND & AIMS: Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to Transglutaminase 6 (TG6) increases the risk of neurologic defects in patients with a new diagnosis of celiac disease. METHODS: We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging of the brain, magnetic resonance (MR) spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction. RESULTS: Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from magnetic resonance imaging, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients-these patients had significant atrophy of subcortical brain regions compared with patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later. CONCLUSIONS: In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurologic deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurologic manifestations among clinicians, and reinforcement of adherence to a strict GFD by patients to avoid permanent neurologic disability.

6.
Comput Med Imaging Graph ; 74: 12-24, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30921550

RESUMO

BACKGROUND: The differential quantification of brain atrophy, white matter hyperintensities (WMH) and stroke lesions is important in studies of stroke and dementia. However, the presence of stroke lesions is usually overlooked by automatic neuroimage processing methods and the-state-of-the-art deep learning schemes, which lack sufficient annotated data. We explore the use of radiomics in identifying whether a brain magnetic resonance imaging (MRI) scan belongs to an individual that had a stroke or not. MATERIALS AND METHODS: We used 1800 3D sets of MRI data from three prospective studies: one of stroke mechanisms and two of cognitive ageing, evaluated 114 textural features in WMH, cerebrospinal fluid, deep grey and normal-appearing white matter, and attempted to classify the scans using a random forest and support vector machine classifiers with and without feature selection. We evaluated the discriminatory power of each feature independently in each population and corrected the result against Type 1 errors. We also evaluated the influence of clinical parameters in the classification results. RESULTS: Subtypes of ischaemic strokes (i.e. lacunar vs. cortical) cannot be discerned using radiomics, but the presence of a stroke-type lesion can be ascertained with accuracies ranging from 0.7 < AUC < 0.83. Feature selection, tissue type, stroke subtype and MRI sequence did not seem to determine the classification results. From all clinical variables evaluated, age correlated with the proportion of images classified correctly using either different or the same descriptors (Pearson r = 0.31 and 0.39 respectively, p < 0.001). CONCLUSIONS: Texture features in conventionally automatically segmented tissues may help in the identification of the presence of previous stroke lesions on an MRI scan, and should be taken into account in transfer learning strategies of the-state-of-the-art deep learning schemes.

7.
Neuroophthalmology ; 43(1): 3-9, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30723518

RESUMO

A recent study found that increased optic canal area on magnetic resonance imaging was associated with worse papilloedema in idiopathic intracranial hypertension (IIH). We repeated this study using more accurate computerized tomography derived measurements. Optic canal dimensions were measured from 42 IIH patients and 24 controls.  These were compared with papilloedema grade.  There was no correlation between any of the optic canal measurements and papilloedema grade and no significant difference in optic canal measurements between patients and controls. Our results cast doubt on the existing literature regarding the association between optic canal size and the degree of papilloedema in IIH. CT delineates bony anatomy more accurately than MRI and our CT-derived optic canal measurements cast doubt on the existing literature regarding the association between optic canal size and the degree of Papilloedema in IIH.

8.
Mol Biol Evol ; 35(10): 2499-2511, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169693

RESUMO

Choanoflagellates and filastereans are the closest known single celled relatives of Metazoa within Holozoa and provide insight into how animals evolved from their unicellular ancestors. Codon usage bias has been extensively studied in metazoans, with both natural selection and mutation pressure playing important roles in different species. The disparate nature of metazoan codon usage patterns prevents the reconstruction of ancestral traits. However, traits conserved across holozoan protists highlight characteristics in the unicellular ancestors of Metazoa. Presented here are the patterns of codon usage in the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta, as well as the filasterean Capsaspora owczarzaki. Codon usage is shown to be remarkably conserved. Highly biased genes preferentially use GC-ending codons, however there is limited evidence this is driven by local mutation pressure. The analyses presented provide strong evidence that natural selection, for both translational accuracy and efficiency, dominates codon usage bias in holozoan protists. In particular, the signature of selection for translational accuracy can be detected even in the most weakly biased genes. Biased codon usage is shown to have coevolved with the tRNA species, with optimal codons showing complementary binding to the highest copy number tRNA genes. Furthermore, tRNA modification is shown to be a common feature for amino acids with higher levels of degeneracy and highly biased genes show a strong preference for using modified tRNAs in translation. The translationally optimal codons defined here will be of benefit to future transgenics work in holozoan protists, as their use should maximise protein yields from edited transgenes.


Assuntos
Coanoflagelados/genética , Códon , Animais , Expressão Gênica , Mutação , RNA de Transferência/genética , Seleção Genética
9.
Front Neurol ; 9: 1147, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30671015

RESUMO

Background and Purpose: The T1-weighted dynamic contrast enhanced (DCE)-MRI is an imaging technique that provides a quantitative measure of pharmacokinetic (PK) parameters characterizing microvasculature of tissues. For the present study, we propose a new machine learning (ML) based approach to directly estimate the PK parameters from the acquired DCE-MRI image-time series that is both more robust and faster than conventional model fitting. Materials and Methods: We specifically utilize deep convolutional neural networks (CNNs) to learn the mapping between the image-time series and corresponding PK parameters. DCE-MRI datasets acquired from 15 patients with clinically evident mild ischaemic stroke were used in the experiments. Training and testing were carried out based on leave-one-patient-out cross- validation. The parameter estimates obtained by the proposed CNN model were compared against the two tracer kinetic models: (1) Patlak model, (2) Extended Tofts model, where the estimation of model parameters is done via voxelwise linear and nonlinear least squares fitting respectively. Results: The trained CNN model is able to yield PK parameters which can better discriminate different brain tissues, including stroke regions. The results also demonstrate that the model generalizes well to new cases even if a subject specific arterial input function (AIF) is not available for the new data. Conclusion: A ML-based model can be used for direct inference of the PK parameters from DCE image series. This method may allow fast and robust parameter inference in population DCE studies. Parameter inference on a 3D volume-time series takes only a few seconds on a GPU machine, which is significantly faster compared to conventional non-linear least squares fitting.

11.
Front Neurol ; 8: 327, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28769863

RESUMO

OBJECTIVES: We evaluate the alternative use of texture analysis for evaluating the role of blood-brain barrier (BBB) in small vessel disease (SVD). METHODS: We used brain magnetic resonance imaging from 204 stroke patients, acquired before and 20 min after intravenous gadolinium administration. We segmented tissues, white matter hyperintensities (WMH) and applied validated visual scores. We measured textural features in all tissues pre- and post-contrast and used ANCOVA to evaluate the effect of SVD indicators on the pre-/post-contrast change, Kruskal-Wallis for significance between patient groups and linear mixed models for pre-/post-contrast variations in cerebrospinal fluid (CSF) with Fazekas scores. RESULTS: Textural "homogeneity" increase in normal tissues with higher presence of SVD indicators was consistently more overt than in abnormal tissues. Textural "homogeneity" increased with age, basal ganglia perivascular spaces scores (p < 0.01) and SVD scores (p < 0.05) and was significantly higher in hypertensive patients (p < 0.002) and lacunar stroke (p = 0.04). Hypertension (74% patients), WMH load (median = 1.5 ± 1.6% of intracranial volume), and age (mean = 65.6 years, SD = 11.3) predicted the pre/post-contrast change in normal white matter, WMH, and index stroke lesion. CSF signal increased with increasing SVD post-contrast. CONCLUSION: A consistent general pattern of increasing textural "homogeneity" with increasing SVD and post-contrast change in CSF with increasing WMH suggest that texture analysis may be useful for the study of BBB integrity.

12.
Neuroradiology ; 59(10): 951-962, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28815362

RESUMO

PURPOSE: Quantitative assessment of white matter hyperintensities (WMH) on structural Magnetic Resonance Imaging (MRI) is challenging. It is important to harmonise results from different software tools considering not only the volume but also the signal intensity. Here we propose and evaluate a metric of white matter (WM) damage that addresses this need. METHODS: We obtained WMH and normal-appearing white matter (NAWM) volumes from brain structural MRI from community dwelling older individuals and stroke patients enrolled in three different studies, using two automatic methods followed by manual editing by two to four observers blind to each other. We calculated the average intensity values on brain structural fluid-attenuation inversion recovery (FLAIR) MRI for the NAWM and WMH. The white matter damage metric is calculated as the proportion of WMH in brain tissue weighted by the relative image contrast of the WMH-to-NAWM. The new metric was evaluated using tissue microstructure parameters and visual ratings of small vessel disease burden and WMH: Fazekas score for WMH burden and Prins scale for WMH change. RESULTS: The correlation between the WM damage metric and the visual rating scores (Spearman ρ > =0.74, p < 0.0001) was slightly stronger than between the latter and WMH volumes (Spearman ρ > =0.72, p < 0.0001). The repeatability of the WM damage metric was better than WM volume (average median difference between measurements 3.26% (IQR 2.76%) and 5.88% (IQR 5.32%) respectively). The follow-up WM damage was highly related to total Prins score even when adjusted for baseline WM damage (ANCOVA, p < 0.0001), which was not always the case for WMH volume, as total Prins was highly associated with the change in the intense WMH volume (p = 0.0079, increase of 4.42 ml per unit change in total Prins, 95%CI [1.17 7.67]), but not with the change in less-intense, subtle WMH, which determined the volumetric change. CONCLUSION: The new metric is practical and simple to calculate. It is robust to variations in image processing methods and scanning protocols, and sensitive to subtle and severe white matter damage.


Assuntos
Envelhecimento/patologia , Encéfalo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , Idoso , Feminino , Humanos , Masculino , Software
13.
Neurology ; 89(10): 1003-1010, 2017 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-28794252

RESUMO

OBJECTIVE: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study. METHODS: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression. RESULTS: Among 190 participants (mean age 65.3 years, range 34.3-96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (ß = 0.0053, 95% confidence interval [CI] 0.00099-0.0097 fewer WMH per 1-mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (ß = 0.075, 95% CI 0.0025-0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, ß = 0.27, 95% CI 0.047-0.50 more WMH per event, p = 0.018). CONCLUSIONS: Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/fisiopatologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Imagem de Tensor de Difusão , Progressão da Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento , Substância Branca/fisiopatologia
14.
Clin Sci (Lond) ; 131(13): 1465-1481, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28468952

RESUMO

In the brain, enlarged perivascular spaces (PVS) relate to cerebral small vessel disease (SVD), poor cognition, inflammation and hypertension. We propose a fully automatic scheme that uses a support vector machine (SVM) to classify the burden of PVS in the basal ganglia (BG) region as low or high. We assess the performance of three different types of descriptors extracted from the BG region in T2-weighted MRI images: (i) statistics obtained from Wavelet transform's coefficients, (ii) local binary patterns and (iii) bag of visual words (BoW) based descriptors characterizing local keypoints obtained from a dense grid with the scale-invariant feature transform (SIFT) characteristics. When the latter were used, the SVM classifier achieved the best accuracy (81.16%). The output from the classifier using the BoW descriptors was compared with visual ratings done by an experienced neuroradiologist (Observer 1) and by a trained image analyst (Observer 2). The agreement and cross-correlation between the classifier and Observer 2 (κ = 0.67 (0.58-0.76)) were slightly higher than between the classifier and Observer 1 (κ = 0.62 (0.53-0.72)) and comparable between both the observers (κ = 0.68 (0.61-0.75)). Finally, three logistic regression models using clinical variables as independent variable and each of the PVS ratings as dependent variable were built to assess how clinically meaningful were the predictions of the classifier. The goodness-of-fit of the model for the classifier was good (area under the curve (AUC) values: 0.93 (model 1), 0.90 (model 2) and 0.92 (model 3)) and slightly better (i.e. AUC values: 0.02 units higher) than that of the model for Observer 2. These results suggest that, although it can be improved, an automatic classifier to assess PVS burden from brain MRI can provide clinically meaningful results close to those from a trained observer.


Assuntos
Gânglios da Base/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Máquina de Vetores de Suporte , Idoso , Atrofia , Gânglios da Base/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia
15.
Trials ; 18(1): 78, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222778

RESUMO

BACKGROUND: White matter hyperintensities (WMHs) are commonly seen on in brain imaging and are associated with stroke and cognitive decline. Therefore, they may provide a relevant intermediate outcome in clinical trials. WMH can be measured as a volume or visually on the Fazekas scale. We investigated predictors of WMH progression and design of efficient studies using WMH volume and Fazekas score as an intermediate outcome. METHODS: We prospectively recruited 264 patients with mild ischaemic stroke and measured WMH volume, Fazekas score, age and cardiovascular risk factors at baseline and 1 year. We modelled predictors of WMH burden at 1 year and used the results in sample size calculations for hypothetical randomised controlled trials with different analysis plans and lengths of follow-up. RESULTS: Follow-up WMH volume was predicted by baseline WMH: a 0.73-ml (95% CI 0.65-0.80, p < 0.0001) increase per 1-ml baseline volume increment, and a 2.93-ml increase (95% CI 1.76-4.10, p < 0.0001) per point on the Fazekas scale. Using a mean difference of 1 ml in WMH volume between treatment groups, 80% power and 5% alpha, adjusting for all predictors and 2-year follow-up produced the smallest sample size (n = 642). Other study designs produced samples sizes from 2054 to 21,270. Sample size calculations using Fazekas score as an outcome with the same power and alpha, as well as an OR corresponding to a 1-ml difference, were sensitive to assumptions and ranged from 2504 to 18,886. CONCLUSIONS: Baseline WMH volume and Fazekas score predicted follow-up WMH volume. Study size was smallest using volumes and longer-term follow-up, but this must be balanced against resources required to measure volumes versus Fazekas scores, bias due to dropout and scanner drift. Samples sizes based on Fazekas scores may be best estimated with simulation studies.


Assuntos
Leucoencefalopatias/diagnóstico por imagem , Imagem por Ressonância Magnética , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tamanho da Amostra , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Fatores Etários , Idoso , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Humanos , Leucoencefalopatias/fisiopatologia , Leucoencefalopatias/psicologia , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Fatores de Tempo , Substância Branca/fisiopatologia
16.
J Cereb Blood Flow Metab ; 37(2): 644-656, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26933133

RESUMO

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage mediates small vessel disease-related brain damage.


Assuntos
Hipertensão/patologia , Doenças Vasculares/patologia , Substância Branca/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Anisotropia , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Doenças Vasculares/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
17.
Br J Radiol ; 90(1069): 20160495, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27858468

RESUMO

OBJECTIVE: To assess the usefulness of arterial spin labelling (ASL) compared with dynamic susceptibility contrast (DSC) perfusion MRI for typical paediatric neuroimaging applications at 1.5 T. METHODS: 52 children (age: 4 months-17 years) with a variety of neurological disorders were scanned using three-dimensional ASL and echoplanar imaging DSC sequences. All images were reviewed by an experienced neuroradiologist; image quality was recorded as "good", "acceptable" or "poor" and diagnostic value was noted as being "greater", "similar" or "less" for ASL when compared with DSC. RESULTS: ASL cerebral blood flow (CBF) images were judged to be acceptable in 89% of cases, poor in 11% of cases and good in 0% of cases, while DSC CBF images were acceptable in 88% of cases, poor in 12% of cases and good in 0% of cases. ASL images were judged to have better diagnostic value than DSC images in 28% of cases, about the same in 58% of cases and worse in 14% of cases. CONCLUSION: The results of this study suggest that ASL offers a realistic alternative to DSC in the paediatric setting for the majority of cases encountered in this study. However, there are some situations where DSC outperforms ASL; so, care is required to choose the most appropriate technique for the pathology under investigation. A larger study is required to corroborate these preliminary findings. Advances in knowledge: ASL is a relatively new perfusion imaging technique whose use has not been explored extensively in the paediatric setting. This work is a preliminary study to evaluate its usefulness in paediatric neuroimaging.


Assuntos
Encefalopatias/diagnóstico , Angiografia Cerebral/métodos , Angiografia por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Adolescente , Neoplasias Encefálicas/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Lactente , Masculino , Pediatria , Estudos Prospectivos , Pesquisa Qualitativa , Marcadores de Spin
18.
Prenat Diagn ; 36(13): 1225-1232, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27862111

RESUMO

OBJECTIVE: Interpretation of magnetic resonance (MR) imaging of the fetal brain in utero is primarily undertaken using 2D images to provide anatomical information about structural abnormalities. It is now possible to obtain 3D image acquisitions that allow measurement of fetal brain volumes that are potentially useful clinically. The aim of our current work is to provide reference values of total brain volumes obtained from a cohort of low risk fetuses with no abnormalities on ante-natal ultrasonography and in utero MR imaging. METHOD: Images from volume MR acquisitions of 132 fetuses were used to extract brain volumes by manual segmentation. Reproducibility and reliability were assessed by analysis of the results of two subgroups who had repeated measurements made by the primary and a secondary observer. RESULTS: Intra-observer and inter-observer agreement was high with no statistically significant differences between and within observers (p = 0.476 and p = 0.427, respectively). The results of the brain volume assessments are presented graphically with mean and 95% prediction limits alongside estimates of normal growth rates. CONCLUSION: We have shown that fetal brain volumes can be reliably extracted from in utero MR (iuMR) imaging 3D datasets with a high degree of reproducibility. The resultant data could potentially be used as a reference tool in the clinical setting. © 2016 John Wiley & Sons, Ltd.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/embriologia , Feto/diagnóstico por imagem , Imagem Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Feminino , Idade Gestacional , Humanos , Variações Dependentes do Observador , Gravidez , Valores de Referência , Reprodutibilidade dos Testes , Ultrassonografia Pré-Natal
19.
Med Phys ; 43(6): 3071-3079, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27277054

RESUMO

PURPOSE: This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. METHODS: A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. RESULTS: Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. CONCLUSIONS: The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth.

20.
Neuroradiology ; 58(5): 475-85, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26833053

RESUMO

INTRODUCTION: Subtle inhomogeneities in the scanner's magnetic fields (B0 and B1) alter the intensity levels of the structural magnetic resonance imaging (MRI) affecting the volumetric assessment of WMH changes. Here, we investigate the influence that (1) correcting the images for the B1 inhomogeneities (i.e. bias field correction (BFC)) and (2) selection of the WMH change assessment method can have on longitudinal analyses of WMH progression and discuss possible solutions. METHODS: We used brain structural MRI from 46 mild stroke patients scanned at stroke onset and 3 years later. We tested three BFC approaches: FSL-FAST, N4 and exponentially entropy-driven homomorphic unsharp masking (E(2)D-HUM) and analysed their effect on the measured WMH change. Separately, we tested two methods to assess WMH changes: measuring WMH volumes independently at both time points semi-automatically (MCMxxxVI) and subtracting intensity-normalised FLAIR images at both time points following image gamma correction. We then combined the BFC with the computational method that performed best across the whole sample to assess WMH changes. RESULTS: Analysis of the difference in the variance-to-mean intensity ratio in normal tissue between BFC and uncorrected images and visual inspection showed that all BFC methods altered the WMH appearance and distribution, but FSL-FAST in general performed more consistently across the sample and MRI modalities. The WMH volume change over 3 years obtained with MCMxxxVI with vs. without FSL-FAST BFC did not significantly differ (medians(IQR)(with BFC) = 3.2(6.3) vs. 2.9(7.4)ml (without BFC), p = 0.5), but both differed significantly from the WMH volume change obtained from subtracting post-processed FLAIR images (without BFC)(7.6(8.2)ml, p < 0.001). This latter method considerably inflated the WMH volume change as subtle WMH at baseline that became more intense at follow-up were counted as increase in the volumetric change. CONCLUSIONS: Measurement of WMH volume change remains challenging. Although the overall volumetric change was not significantly affected by the application of BFC, these methods distorted the image intensity distribution affecting subtle WMH. Subtracting the FLAIR images at both time points following gamma correction seems a promising technique but is adversely affected by subtle WMH. It is important to take into account not only the changes in volume but also in the signal intensity.


Assuntos
Imagem por Ressonância Magnética/métodos , Acidente Vascular Cerebral/patologia , Substância Branca/patologia , Idoso , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
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